Multidisciplinary approach to the complex treatment for non-cirrhotic portal hypertension – case-report-based discussion

Abstract

Non-cirrhotic portal vein thrombosis (PVT) in patients with antiphospholipid syndrome (APS) is a rare complication, and the management has to be determined individually based on the extent and severity of the presentation. We report on a 37-year-old male patient with non-cirrhotic chronic PVT related to a severe thrombophilia, comprising APS, antithrombin-, factor V- and factor X-deficiency. Three years after the initial diagnosis of non-cirrhotic PVT, the patient presented with severe hemorrhagic shock related to acute bleeding from esophageal varices, requiring an emergency transjugular intrahepatic portosystemic stent shunt (TIPSS). TIPSS was revised after a recurrent bleeding episode due to insufficient reduction of the portal pressure. Additionally, embolization of the dilated V. coronaria ventriculi led to the regression of esophageal varices but resulted simultaneously in a left-sided portal hypertension (LSPH) with development of stomach wall and perisplenic varices. After a third episode of acute esophageal varices bleeding, a surgical distal splenorenal shunt (Warren shunt) was performed to reduce the LSPH. Despite anticoagulation with low molecular weight heparin and antithrombin substitution, endoluminal thrombosis led to a complete Warren shunt occlusion, aggravating the severe splenomegaly and pancytopenia. Finally, a partial spleen embolization (PSE) was performed. In the postinterventional course, leukocyte and platelet counts increased rapidly and the patient showed no further bleeding episodes. Overall, this complex course demonstrates the need for individual assessment of multimodal treatment options in non-cirrhotic portal hypertension. This young patient required triple modality porto-systemic pressure reduction (TIPSS, Warren shunt, PSE) and involved finely balanced anticoagulation and bleeding control.

Zusammenfassung

Die nicht-zirrhotische Pfortaderthrombose (PT) im Rahmen eines Antiphospholipid-Syndroms (APS) stellt eine seltene Komplikation dar. Je nach Ausmaß und Schweregrad muss die Therapie individuell angepasst werden. Diese Kasuistik beschreibt den Fall eines 37-jährigen männlichen Patienten mit nicht-zirrhotischer, chronischer PT aufgrund einer schweren Thrombophilie, die ein APS sowie ein Antithrombin-, Faktor V- und Faktor X-Mangel umfasst.

Drei Jahre nach der Erstdiagnose der nicht-zirrhotischen PT, zeigte der Patient einen schweren hämorrhagischen Schock aufgrund einer Ösophagusvarizenblutung, die die notfallmäßige Anlage eines transjugulären intrahepatischen portosystemischen stent shunts (TIPSS) notwendig machte. Nach einer Rezidivblutung aufgrund einer unzureichenden Senkung des portalvenösen Drucks erfolgte die TIPSS-Revision. Die Embolisation der stark dilatierten V. coronaria ventriculi führte zum Rückgang der Ösophagusvarizen, resultierte jedoch gleichzeitig in einer sektoralen portalen Hypertension im linken Oberbauch mit Entwicklung von Magenwand- und perisplenischen Varizen. Nach einer dritten Blutungsepisode erfolgte der Entscheid zur Anlage eines distalen splenorenalen shunts (Warren shunt) zur Reduktion der sektoralen Hypertension. Trotz Antikoagulation mit niedermolekularen Heparinen und Antithrombin-Substitution, entwickelte der Patient eine vollständige endoluminale Shunt-Thrombose, die die schwere Splenomegalie und Panzytopenie weiter aggravierte. Schließlich erfolgte eine Milz-Teilembolisation. Postinterventionell stiegen die Leukozyten und Thrombozyten rasch an und der Patient zeigte keine weitere Blutungsepisode. Zusammenfassend zeigt dieser komplexe Fall die Notwendigkeit der individuellen Abwägung der multimodalen Therapieoptionen im Rahmen einer nicht-zirrhotischen portalen Hypertension. Dieser junge Patient benötigte eine trimodale porto-systemische Druckreduktion (TIPSS, Warren shunt, Milz-Teilembolisation) und eine sorgfältig balancierte Antikoagulation zur Blutungskontrolle.

Key words

portal vein thrombosis - antiphospholipid syndrome - esophageal varices bleeding - TIPSS - splenorenal shunt - left-sided portal hypertension - pancytopenia - splenomegaly - partial spleen embolization - bleeding control

Schlüsselwörter

Pfortaderthrombose - Antiphospholipid-Syndrom - Ösophagusvarizenblutung - TIPSS - Splenorenaler Shunt - Sektorale portale Hypertension im linken Oberbauch - Panzytopenie - Splenomegalie - Milzteilembolisation - Blutungskontrolle

• References

• 1 Intagliata NM, Caldwell SH, Tripodi A. Diagnosis, development, and treatment of portal vein thrombosis in patients with and without cirrhosis. Gastroenterology 2019; 156: 1582-1599.e1 . doi:10.1053/j.gastro.2019.01.265
• 2 Plessier A, Darwish-Murad S, Hernandez-Guerra M. et al Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow-up study. Hepatology 2010; 51: 210-218 . doi:10.1002/hep.23259
• 3 Tremblay D, Naymagon L, Troy K. et al The utility of thrombophilia testing in patients with newly diagnosed portal vein thrombosis. Blood Coagul Fibrinolysis 2020; 31: 213-218 . doi:10.1097/MBC.0000000000000901
• 4 Cervera R. Antiphospholipid syndrome. Thrombosis Research 2017; 151: S43-S47 . doi:10.1016/S0049-3848(17)30066-X
• 5 Miyakis S, Lockshin MD, Atsumi T. et al International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4: 295-306 . doi:10.1111/j.1538-7836.2006.01753.x
• 6 Petri M. Epidemiology of the antiphospholipid antibody syndrome. J Autoimmun 2000; 15: 145-151 . doi:10.1006/jaut.2000.0409
• 7 Noronha Ferreira C, Seijo S, Plessier A. et al Natural history and management of esophagogastric varices in chronic noncirrhotic, nontumoral portal vein thrombosis. Hepatology 2016; 63: 1640-1650 . doi:10.1002/hep.28466
• 8 Rajani R, Björnsson E, Bergquist A. et al The epidemiology and clinical features of portal vein thrombosis: a multicentre study. Aliment Pharmacol Ther 2010; 32: 1154-1162 . doi:10.1111/j.1365-2036.2010.04454.x
• 9 Spaander MCW, Hoekstra J, Hansen BE. et al Anticoagulant therapy in patients with non-cirrhotic portal vein thrombosis: effect on new thrombotic events and gastrointestinal bleeding. J Thromb Haemost 2013; 11: 452-459 . doi:10.1111/jth.12121
• 10 Amitrano L, Guardascione MA, Scaglione M. et al Prognostic factors in noncirrhotic patients with splanchnic vein thromboses. Am J Gastroenterol 2007; 102: 2464-2470 . doi:10.1111/j.1572-0241.2007.01477.x
• 11 Orr DW, Harrison PM, Devlin J. et al Chronic mesenteric venous thrombosis: evaluation and determinants of survival during long-term follow-up. Clin Gastroenterol Hepatol 2007; 5: 80-86 . doi:10.1016/j.cgh.2006.09.030
• 12 Condat B, Pessione F, Helene Denninger M. et al Recent portal or mesenteric venous thrombosis: increased recognition and frequent recanalization on anticoagulant therapy. Hepatology 2000; 32: 466-470 . doi:10.1053/jhep.2000.16597
• 13 European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Vascular diseases of the liver. J Hepatol 2016; 64: 179-202 . doi:10.1016/j.jhep.2015.07.040
• 14 Gerwing M, Wilms C, Heinzow H. et al Escalating interventional recanalization therapy in non-cirrhotic, non-malignant acute portal vein thrombosis. Eur J Gastroenterol Hepatol 2019; 31: 1584-1591 . doi:10.1097/MEG.0000000000001559
• 15 Köklü S, Coban S, Yüksel O. et al Left-sided portal hypertension. Dig Dis Sci 2007; 52: 1141-1149 . doi:10.1007/s10620-006-9307-x
• 16 Madsen MS, Petersen TH, Sommer H. Segmental portal hypertension. Ann Surg 1986; 204: 72-77 . doi:10.1097/00000658-198607000-00010
• 17 Evans GR, Yellin AE, Weaver FA. et al Sinistral (left-sided) portal hypertension. Am Surg 1990; 56: 758-763
• 18 Yale CE, Crummy AB. Splenic vein thrombosis and bleeding esophageal varices. JAMA 1971; 217: 317-320
• 19 Livingstone AS, Koniaris LG, Perez EA. et al 507 Warren-Zeppa distal splenorenal shunts: a 34-year experience. Ann Surg 2006; 243: 884-892 ; discussion 892-894 doi:10.1097/01.sla.0000219681.08312.87
• 20 Orloff MJ, Orloff MS, Girard B. et al Bleeding esophagogastric varices from extrahepatic portal hypertension: 40 years’ experience with portal-systemic shunt. J Am Coll Surg 2002; 194: 717-728 . doi:10.1016/S1072-7515(02)01170-5
• 21 Sretenović A, Perisić V, Vujović D. et al Warren shunt combined with partial splenectomy in children with extra-hepatic portal hypertension, massive splenomegaly and severe hypersplenism. Srp Arh Celok Lek 2014; 142: 419-423
• 22 Galindo M, Khamashta MA, Hughes GR. Splenectomy for refractory thrombocytopenia in the antiphospholipid syndrome. Rheumatology (Oxford) 1999; 38: 848-853 . doi:10.1093/rheumatology/38.9.848
• 23 Law DK, Moore EE. Compartmentalized gastrosplenic and mesenteric venous hypertension after distal splenorenal shunt occlusion: response to mesocaval shunt and splenectomy. Surgery 1979; 85: 579-582
• 24 Zhao Y, Guo L, Huang Q. et al Observation of immediate and mid-term effects of partial spleen embolization in reducing hepatic venous pressure gradient. Medicine (Baltimore) 2019; 98: e17900 . doi:10.1097/MD.0000000000017900
• 25 Zhu K, Meng X, Qian J. et al Partial splenic embolization for hypersplenism in cirrhosis: a long-term outcome in 62 patients. Dig Liver Dis 2009; 41: 411-416 . doi:10.1016/j.dld.2008.10.005
• 26 Matsumoto T, Yamagami T, Terayama K. et al Risk factors and clinical course of portal and/or splenic vein thrombosis after partial splenic embolization. Acta Radiol 2009; 50: 617-623 . doi:10.1080/02841850902922779
• 27 Connors JM. Thrombophilia Testing and Venous Thrombosis. N Engl J Med 2017; 377: 1177-1187 . doi:10.1056/NEJMra1700365
• 28 Denninger MH, Chaït Y, Casadevall N. et al Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors. Hepatology 2000; 31: 587-591 . doi:10.1002/hep.510310307
• 29 Janssen HL, Meinardi JR, Vleggaar FP. et al Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study. Blood 2000; 96: 2364-2368
• 30 Primignani M, Martinelli I, Bucciarelli P. et al Risk factors for thrombophilia in extrahepatic portal vein obstruction. Hepatology 2005; 41: 603-608 . doi:10.1002/hep.20591
• 31 Turnes J, García-Pagán JC, González M. et al Portal hypertension-related complications after acute portal vein thrombosis: impact of early anticoagulation. Clin Gastroenterol Hepatol 2008; 6: 1412-1417 . doi:10.1016/j.cgh.2008.07.031
• 32 Croles FN, Lukens MV, Mulder R. et al Monitoring of heparins in antithrombin-deficient patients. Thrombosis Research 2019; 175: 8-12 . doi:10.1016/j.thromres.2019.01.007
• 33 Garcia D, Erkan D. Diagnosis and management of the antiphospholipid syndrome. N Engl J Med 2018; 378: 2010-2021 . doi:10.1056/NEJMra1705454
• 34 de Franchis R. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63: 743-752 . doi:10.1016/j.jhep.2015.05.022
• 35 McKeage K, Plosker GL. Argatroban. Drugs 2001; 61: 515-522 ; discussion 523-524 doi:10.2165/00003495-200161040-00005